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  Circulating Fibronectin Controls Tumor Growth

von Au, A., Vasel, M., Kraft, S., Sens, C., Hackl, N., Marx, A., et al. (2013). Circulating Fibronectin Controls Tumor Growth. NEOPLASIA, 15(8), 925-938. doi:10.1593/neo.13762.

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 Creators:
von Au, Anja1, Author           
Vasel, Matthaeus1, Author           
Kraft, Sabrina1, Author           
Sens, Carla1, Author           
Hackl, Norman1, Author           
Marx, Alexander2, Author
Stroebel, Philipp2, Author
Hennenlotter, Joerg2, Author
Todenhoefer, Tilman2, Author
Stenzl, Arnulf2, Author
Schott, Sarah2, Author
Sinn, Hans-Peter2, Author
Wetterwald, Antoinette2, Author
Bermejo, Justo Lorenzo2, Author
Cecchini, Marco G.2, Author
Nakchbandi, Inaam A.1, Author           
Affiliations:
1Nakchbandi, Inaam / Translational Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565162              
2external, ou_persistent22              

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Free keywords: ALTERNATIVELY SPLICED SEGMENTS; EXTRACELLULAR-MATRIX; BONE-MARROW; BREAST-CANCER; IN-VIVO; CELL-PROLIFERATION; METASTATIC NICHE; FACTOR-BINDING; BLOOD-VESSELS; MOUSE MODEL
 Abstract: Fibronectin is ubiquitously expressed in the extracellular matrix, and experimental evidence has shown that it modulates blood vessel formation. The relative contribution of local and circulating fibronectin to blood vessel formation in vivo remains unknown despite evidence for unexpected roles of circulating fibronectin in various diseases. Using transgenic mouse models, we established that circulating fibronectin facilitates the growth of bone metastases by enhancing blood vessel formation and maturation. This effect is more relevant than that of fibronectin produced by endothelial cells and pericytes, which only exert a small additive effect on vessel maturation. Circulating fibronectin enhances its local production in tumors through a positive feedback loop and increases the amount of vascular endothelial growth factor (VEGF) retained in the matrix. Both fibronectin and VEGF then cooperate to stimulate blood vessel formation. Fibronectin content in the tumor correlates with the number of blood vessels and tumor growth in the mouse models. Consistent with these results, examination of three separate arrays from patients with breast and prostate cancers revealed that a high staining intensity for fibronectin in tumors is associated with increased mortality. These results establish that circulating fibronectin modulates blood vessel formation and tumor growth by modifying the amount of and the response to VEGF. Furthermore, determination of the fibronectin content can serve as a prognostic biomarker for breast and prostate cancers and possibly other cancers.

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Language(s): eng - English
 Dates: 2013-08
 Publication Status: Issued
 Pages: 20
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000324488800006
DOI: 10.1593/neo.13762
 Degree: -

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Title: NEOPLASIA
Source Genre: Journal
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Publ. Info: 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA : NEOPLASIA PRESS
Pages: - Volume / Issue: 15 (8) Sequence Number: - Start / End Page: 925 - 938 Identifier: ISSN: 1522-8002